PEDIATRIC PATHOLOGY WARM-UP ANSWERS 1. Answer A. Whenever you are fACeD with an ovarian tumor, it’s CritiCal that you Keep these 4 Categories in minD. By the enD of your first year of training, you shoulD be able to Conjure a list of entities for eACh Category: 1) Germ cell tumors: Dysgerminoma, yolK sAC tumor, embryonal CarCinoma, mature teratoma, immature teratoma, ChorioCarCinoma; 2) Sex cord stromal tumors: Sertoli-LeyDig Cell tumors, granulosa Cell tumors, fibroma, theComa, the weirD one Known as “sex CorD tumor with annular tubules” (SCTAT); 3) Epithelial tumors: Serous, Clear Cell, muCinous, enDometrioiD, anD Brenner tumors. Of Course Don’t forget metastasis; “KruKenberg tumors” from the GI trACt are a favorite from this Camp but Don’t forget breast, Cervix, enDometrium, anD so forth. You Can loosely “triage” items on your Differential Diagnosis baseD on patient age: germ Cell tumors are the most Common ovarian neoplasms in young ChilDren anD ADolesCents, while stromal tumors have a peAK inCiDenCe in early anD miDDle ADulthooD anD epithelial tumors are most Common in miDDle-ageD anD olDer women. Just remember that these rules aren’t written in stone: College stuDents get serous ovarian CarCinomas, nursing home resiDents get juvenile granulosa Cell tumors, etc. 2. Answer E. This question brings up some important terminology for approAChing peDiatriC pathology, mainly the broAD Categories of “small round blue cell tumors” anD “embryonic tumors.” Do you thinK that the term “small rounD blue Cell tumor” (SRBCT) is equivalent to “embryoniC tumor?” It’s not, although there is signifiCant overlap between the tumors enCompasseD in eACh Category. First, Know that SRBCT is not a Diagnosis, it’s a pattern. As the name inDiCates, SRBCT refers to tumors CompriseD of relatively uniform, primitive-appearing Cells with rounD nuClei anD little Cytoplasm. It’s worth noting that the Cells often aren’t all that small! A broAD Differential for a SRBCT might inCluDe neuroblastoma, meDulloblastoma, retinoblastoma, Ewings/PNET, CLL/SLL, large Cell lymphoma, DesmoplastiC small rounD Cell tumor, embryonal rhabDomyosarComas, mesenChymal ChonDrosarComa, even neuroenDoCrine tumors liKe small Cell lung CarCinoma anD MerCKel Cell CarCinoma. “EmbryoniC tumors,” on the other hanD, reCapitulate tissues seen in the Developing embryo. While this often manifests in a SRBCT appearanCe, suCh as with neuroblastoma, meDulloblastoma, retinoblastoma, anD embryonal rhabDomyosarComa, this is not always the Case. Wilms tumor anD hepatoblastoma, for instanCe, are embryoniC tumors whiCh only rarely show SRBCT histology. PanCreatoblastoma is an embryoniC tumor whiCh Can have a heterogeneous morphology quite DistinCt from the SRBCT pattern! (See Challenge question #43). While true “embryoniC tumors” are largely restriCteD to young ChilDren (usually first few years of life), the SRBCT Differential Comes up ACross all age ranges. 3. False. Remember from your peDiatriC rotation in meD sChool, “ChilDren are NOT just little ADults!” The same ADage applies to their CanCers! For instanCe, the Weiss Criteria are valuable for Differentiating ADrenal CortiCal ADenomas from CarCinomas in ADults, but have no proven utility in iDentiCal tumors from KiDs. PeDiatriC gastrointestinal stromal tumors (GISTs) are quite Different beasts from their ADult Counterparts. The list goes on! 4. Answer A. Although we might ConsiDer Ewing sarComa if the lesion was unifoCal anD limiteD to the bone, the presenCe of an ADrenal mass points us towarDs neuroblastoma. Metastasis at presentation is unfortunately quite Common for neuroblastomas, so bone involvement shoulD not surprise us. Also, this patient is on the young siDe for Ewings sarComa (although it CoulD Certainly happen). PheoChromoCytoma woulD Come to minD for an ADrenal tumor in an older patient, but is not a small rounD blue Cell tumor anD is metastatiC in a minority of Cases. Wilm’s tumors arise in the KiDney, although when tumors are large it Can sometimes be DiffiCult to Determine whether they originate in the KiDney or the ADrenal. Wilm’s tumor Does not tenD to metastasize to bones (it prefers the “3 L’s” … see Challenge questions #36-37 for Details). 5. Answer A. If you went for Wilm’s tumor Don’t beat yourself up, beCause this is the most Common renal neoplasm in young chilDren after 2 months of age. However, in the immeDiate neonatal perioD the most Common neoplasm is congenital meosblasic nephroma, a usually benign tumor of the renal mesenChyma. The answer ChoiCes are listeD in orDer of DeCreasing frequenCy. Note that I speCifiCally asKeD for the most Common neoplasm, sinCe the vast majority of renal masses in newborns are relateD to hyDronephrosis or multiCystiC Dysplasia. PEDIATRIC PATHOLOGY CHALLENGE ANSWERS 1. Answer A. PAS-positive seCretions are not a feature of monophasiC synovial sarComa (SS) although they Can be seen in assoCiation with the glanDular elements of biphasiC synovial sarComa. Although you might have guesseD that monophasiC SS by Definition lACKs epithelial elements, Don’t be fooleD! While not glaringly eviDent on H&E stain, small epithelioiD Clusters are often revealeD by CytoKeratin staining of monophasiC SS. Both monophasiC anD biphasiC variants may show a hemangioperiCytomA-liKe vasCular pattern, anD inDeeD hemangioperiCytoma/solitary fibrous tumor is on the Differential Diagnosis for monophasiC Cases. MiCrovilli are seen in both variants of SS. Finally, the X;18 transloCation with SYT-SSSX1 or SYT-SSX2 fusion is speCifiC for SS. 2. Answer C. Calcified. This is a triCKy question, beCause while early investigations suggesteD that biphasiC SS Carries a better prognosis than its monophasiC Colleague, subsequent stuDies have shown that biphasiC histology Confers no inDepenDent prognosis signifiCanCe. In ADDition, early stuDies suggest SYT-SSX2 was favorable (more Common in biphasiC) but similarly in further stuDies shows no prognostiC signifiCanCe. However, patients with CalCifieD SS (whiCh are often biphasiC) Do have a more favorable outcome. The only other subtype with establisheD prognostiC signifiCanCe is the “poorly-DifferentiateD monophasiC” variant, whiCh is CharACterizeD by larger nuClei anD more inCreaseD mitotiC ACtivity when CompareD to typiCal SS. 3. Answer B. A young ADult patient with Dermal/subCutaneous noDules, espeCially of the Distal arm/wrist, anD histology evoCative of rheumatoiD granulomas shoulD prompt wilDly aggressive red-flag waving in your brain. We’re worrieD about epithelioid sarcoma, whiCh must be exCluDeD before we blow these lesions off as inflammatory. EpithelioiD sarComa is cytokeratin- positive anD INI-negative. Miss it at your—anD the patient’s—peril. While worK-up for infeCtion anD auto-immune proCesses woulD be warranteD if CK is negative, in this setting exClusion of a malignant tumor is the first priority. 4. Answer A. The CliniCal anD histologiC DesCription is Consistent with a glomus tumor. These tumors are thought to be DeriveD from moDifieD smooth musCle Cells Known as periCytes. They are positive for smooth muscle actin anD muscle specific actin but lACK reACtivity for Desmin anD enDothelial Cell marKers. 5. Answer B. Calcifying apopneurotic fibroma. The DesCription is ClassiC for CAF: a painless hanD or foot noDule oCCurring in a ChilD anD CompriseD of mature fibrous bACKgrounD with more primitive fibrosarComA-liKe elements arrangeD in noDules with Central CalCifiCation anD/or ChonDroiD. It’s important to note that infiltration by the mature fibrous Component Does not inDiCate malignanCy. 6. Answer E. The loCation (heAD anD neCK) anD histologiC DesCription are Compatible with a Diagnosis of juvenile xanthogranuloma with its ClassiC (but not neCessary) Touton giant cells. While positive for a variety of histioCytiC/mACrophage marKers (CD68, lysozyme, HAM56, fACtor XIIIa), anD the ubiquitous vimentin, JXGs shoulD not stain with CytoKeratins. 7. Answer D. Alveolar rhadomyosarcomas tenD to oCCur in the trunK anD extremities; heAD anD neCK loCation is more Common for the embryonal subtype. All other statements are true: when CompareD to embryonal tumors, alveolar rhabDomyosarComas Carry a worse prognosis anD are more Common in ADolesCents. ClassiC histology inCluDes alveolar-liKe spACes however these may be absent in a soliD variant. In soliD Cases, the Diagnosis Can be ConfirmeD by the iDentifiCation of multinuCleateD giant Cells with wreatheD nuClei; these shoulD not be seen in embryonal rhaboDmyosarComa. 8. Answer E. Embryonal rhabdomoysarcoma Cells are typiCally moDerate to poorly DifferentiateD, grow in sheets, anD are typifieD by eosinophiliC granular Cytoplasm anD eCCentriC nuClei. Cross striations are not Commonly seen. Although botryoid rhabdomyosarcomas (whiCh is a speCial subtype of embryonal rhabDomyosarComa arising in assoCiation with lumens suCh as the blADDer, genital trACt, anD ConjuCtiva) show the ClassiC Cambium layer unDerlying an epithelium anD myxoiD bACKgrounD, these features are not seen with other embryonal rhabDomyosarComas. The prognosis is relatively favorable in ChilDren anD worse in ADolesCents. While ChilDhooD Cases most Commonly oCCur in the heAD anD neCK, orbit, GU trACt, anD retroperitoneum, ADolesCents tenD to get paratestiCular anD extremity tumors. 9. Answer A. The CliniCal, histologiC, anD immunohistoChemiCal features fit with desmoid fibrosis. These tumors show a female preDominanCe anD most often arise in the abDomen, sometimes following surgery or parity. They are assoCiateD with the autosomal Dominant (AD) Gardeners Syndrome,